A new statistical model for genome-scale MicroRNA target prediction

MicroRNAs regulate virtually the whole gene network in human body and have been implicated in most physiological and pathological conditions including cancers. Understanding the precise mechanisms of microRNA-mRNA interaction is fundamentally important to elucidate the important roles of miRNA in regulating various cellular and disease developmental stages. Numerous computational methods have been developed for miRNA target prediction, mostly focusing on static binding prediction and highly dependent on sequence-pairing interactions. However, the interplay between competing and cooperative microRNA-target binding makes it exceptionally complex and challenging for reliable target identification, which has hindered the existing tools from practical use. In this study, we present a new computational method for microRNA target prediction using the Dirichlet Process Gaussian Mixture Model (DPGMM). A comprehensive collection of features related to sequence and structure of microRNAs, mRNAs, and the binding sites have been assessed to optimize the statistical prediction of new binding sites in human transcriptome. Through multiple evaluations on recently-discovered miRNA-mRNA interactions reported in large-scale sequencing analyses and a screening test on the entire human transcripts, the results show that our model outperformed several state-of-the-art tools in terms of reduced false positive prediction and promising predictive power on binding sites specific to transcript isoforms.